Phosphatidylcholine (PC)-specific phospholipases D (PLDs) catalyze the hydrolysis of PC to produce phosphatidic
acid and choline. A range of agonists acting through G protein-coupled receptors and receptor tyrosine kinases stimulate
this hydrolysis. PC-specific PLD activity has been implicated in numerous cellular pathways, including signal
transduction, membrane trafficking, and the regulation of mitosis. Using primers specific for an EST that showed
similarity to a yeast PC-specific PLD gene, Hammond et al. (1995) performed PCR on HeLa cDNA and then screened a
HeLa cDNA library with the PCR product to clone a cDNA encoding PLD1.
The recombinant PLD1 activity is located both in the cytoplasm and in association with the membrane.
PLD1 is stimulated by phosphatidylinositol 4,5-biphosphate and strongly inhibited by oleate in vitro.
General function
Intracellular signaling cascade
Comment
THE exact PLD gene (1 or 2) in the ovary is still unclear.
Cellular localization
Cytoplasmic
Comment
Ovarian function
Follicle atresia, Germ cell development
Comment
Kim JH examined the role of ceramide as a candidate intracelluar mediator of Fas mediated
signaling in cultured granulosa cells. Exposure of granulosa cells to anti-Fas monoclonal antibody (anti-Fas mAb) resulted in sphingomyelin hydrolysis, which was accompanied by a progressive increase in endogenous levels of ceramide, The addition of exogenous C-6-ceramide induced apoptotic DNA degradation. Furthermore, both anti-Fas mAb and C-6-ceramide decreased phospholipase D (PLD) activity and diacylglycerol (DAG) concentrations in a time- or a dose-dependent manner, In addition, treatment with phorbol 12-myristate 3-acetate completely attenuated the ceramide-induced inhibition of PLD activity and partially suppressed ceramide-induced apoptosis.
Expression regulated by
GnRH
Comment
Liscovitch M, et al. reported that gonadotropin-releasing hormone activates phospholipase D in ovarian granulosa cells. The activation of phospholipase-D (PLD) was implicated in mediating the differentiative
action of GnRH on preovulatory granulosa cells. Amsterdam A et al studied the activation of PLD and the action of its product, phosphatidic acid (PA), in preantral granulosa cells. It is concluded that activation of PLD and the resultant production of PA could mediate
the antidifferentiative action of GnRH in preantral granulosa cells. Moreover, GnRH-induced
PLD-generated signals counteract the FSH-induced cAMP-dependent signals that modulate the
organization of the actin cytoskeleton characteristic of steroidogenic cells.
Ovarian localization
Primordial Germ Cell, Granulosa, Luteal cells
Comment
Yamamoto H et al reported the activation of phospholipase D by prostaglandin F2 alpha in rat luteal cells and effects of inhibitors of arachidonic acid metabolism. It was suggested
that PGF2 alpha-stimulated PLD activation is mediated via lipoxygenase products.
New Candidate Genes Identified for Controlling Mouse Gonadal Sex Determination and the Early Stages of Granulosa and Sertoli Cell Differentiation. Bouma GJ et al. Mammalian gonadal sex determining (GSD) genes are expressed in a unique population of somatic cells that differentiate into granulosa cells in XX gonads or Sertoli cells in XY gonads. The ability to efficiently isolate these somatic support cells (SSCs) during the earliest stages of gonad development would facilitate identifying 1) new candidate GSD genes that may be involved in cases of unexplained abnormal gonad development, and 2) genes involved in the earliest stages of granulosa and Sertoli cell differentiation. We report the development of a unique mouse carrying two transgenes that allow XX and XY mice to be distinguished as early as Embryonic Day (E) 11.5, and allow SSCs to be isolated from undifferentiated (E11.5) and early differentiated (E12.5) fetal gonads. The Mouse Genome 430v2.0 GeneChip (Affymetrix) was used to identify transcripts exhibiting a sexual dimorphic expression pattern in XX and XY isolated SSCs. The analysis revealed previously unidentified sexually dimorphic transcripts, including low-level expressed genes such as Sry, a gene not identified in other microarray studies. Multi-gene real-time PCR analysis of 57 genes verified that 53 were expressed in fetal gonads in a sexually dimorphic pattern, and whole-mount in situ hybridization analysis verified 4930563E18Rik, Pld1, and Sprr2d are expressed in XX gonads, and Fbln2, Ppargc1a, and Scrn1 are expressed in XY gonads. Taken together the data provide a comprehensive resource for the spatial-temporal expression pattern of genes that are part of the genetic network underlying the early stages of mammalian fetal gonadal development, including the development of granulosa and Sertoli cells.